Over the past five years, Biorasis, Inc. has been developing a totally implantable biosensor platform (0.5 x 0.5 x 5 mm) capable of continuously monitoring glucose. The underlying principle in developing this miniaturized sensor hinges on extreme miniaturization utilizing light, both as a powering source and a communication link. Such implant size reduction results in minimal tissue damage during implantation. The localized release of various tissue response modifiers has also afforded effective inflammation control and fibrosis suppression, needed for long-term sensor functionality. The sensing element of this platform is based on a novel 5-layer device architecture that yields high performance in terms of selectivity, linearity, response time and sensitivity. In vivo studies have indicated an aggregate mean absolute relative difference (MARD) value of 11-13% between our sensor-measured glucose levels and reference standards over a period of 14- days. While this is already comparable to the transcutaneous sensors currently in market, our analysis has shown that the sensor MARD values can be further lowered to 5-6% if one takes into consideration the variability within the sensing element to permeability changes that affect the diffusion of glucose and other co- substrates. Objective/Hypothesis: Correlating the response of the glucose sensing element to the permeability changes for glucose and other co-substrates, can substantially improve sensor accuracy (with MARD values down to 5- 6%) for both hypo- and hyperglycemic regions over extended periods of time (3 months). Study Design: This Phase I study will be focused on proof-of-concept demonstration of the fully-integrated device for 1-month in normal and diabetic rats. For this, our current prototype device will be outfitted with a new electronic chip comprising of two additional potentiostats and sensor-select circuitry, along with the three sensing elements. Furthermore, wafer-level integration and packaging of the micro-/optoelectronic components and sensing elements will be carried out for in vivo studies and validation. Relevance: In view of the growing number of diabetics worldwide, there is a tremendous need for devices that provide accurate detection of glucose levels. In lieu of the difficulties associated with glucose monitoring using non-invasive methods, extreme miniaturization of a totally implantable device together with assured accuracy and long-term operation, present a viable alternative. The proposed multi-sensing element platform addresses miniaturization and accurate glucose readings. In addition, the wireless communication and prolonged lifetime render it an effective device for diabetic care as well as a powerful tool for metabolite monitoring in pre-clinical animal research.